Project Summary Glaucoma is a leading cause of blindness both in the US and worldwide. The long-term purpose of this project is to improve functional testing in glaucoma. Assessment and follow-up of patients currently relies on automated perimetry to provide functional testing of the visual field. However, the ability to assess progression and/or response to treatment using perimetry is hampered by high variability, especially in areas of moderate or severe glaucomatous damage. This proposal will build on previous work by our laboratory to reduce the variability, increase the dynamic range, and improve the analysis and interpretation, of these test results. Our experiments are explicitly designed so that their results and conclusions will be rapidly translatable to clinical practice. The project will improve the accuracy, efficiency and utility of functional testing, giving immediate impact in both research and clinical settings, and laying groundwork for the next generation of instruments and algorithms. The first Specific Aim is to use a novel stimulus to extend the effective dynamic range of perimetry and reduce its variability. Current clinical perimetry relies on the test subject pressing a button when they see a stimulus consisting of a small, stationary circle of brighter light on a white background. We propose to use a new stimulus, which we anticipate being easier to detect, allowing reliable measurements to be made in more damaged regions of the visual field than is currently possible, and reducing variability. The second Specific Aim is to better use data from current clinical perimetry. We anticipate being able to detect change sooner when looking for changes in anatomically-based clusters of test locations, rather than considering every location individually or considering all locations simultaneously. We will derive a measure of the rate of change based on this cluster analysis that corresponds with experienced clinicians? opinions of the severity of disease progression, which would aid in the staging and monitoring of disease progression, and hence aid clinical decision making. The third Specific Aim is to perform high-accuracy testing of a subset of visual field locations. The current clinical standard is to instead perform low-accuracy testing of a wider selection of locations. We will compare the ability of these two approaches to detect functional change, and evaluate the effect on the strengths of the cross-sectional and longitudinal correlations with structural measures. The three aims are complementary. It is anticipated that these aims will improve data collection, analysis and interpretation when using perimetry. Such improvements in a test as commonly performed as perimetry will significantly impact future clinical practice.